Keratinocyte-derived, CD80-mediated costimulation is associated with hapten-specific IgE production during contact hypersensitivity to TH1 haptens

Burns, Robert P.; Luzina, Irina G.; Nasir, Adnan; Haidaris, Constantine G.; Barth, Richard K.; Gaspari, Anthony A.

doi:10.1016/j.jaci.2004.11.019

Cited by 18 publications

(17 citation statements)

References 41 publications

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“…Other findings support the conclusion that KC are important for suppressing CHS responses via IL-10 secretion, particularly in response to hapten exposure [57,58]. This cytokine suppresses CHS responses.…”

Section: Kc: a Key Participant In Acdsupporting

confidence: 81%

Allergic Contact Dermatitis

Gober¹,

Gaspari²

2008

Current Directions in Autoimmunity

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Allergic contact dermatitis is a classic example of a cell mediated hypersensitivity reaction in the skin. This occurs as a result of xenobiotic chemicals penetrating into the skin, chemically reacting with self proteins, eventually resulting in a hapten-specific immune response. It is precisely because of this localized immune response that allergic signs and symptoms occur (redness, edema, warmth and pruritus). It has been known for years that conventional T-cells (CD4+ or CD8+ T-cells that express a T-cell receptor alpha/Beta) are critical effectors for this reaction. There is emerging evidence that innate immune lymphocytes such as invariant Natural killer T-cells and even Natural killer cells may play important role. Other T-cell types such as Tregulatory cells and the IL-10 secreting Tregulatory cells type I are likely to be important in the control (resolution) of allergic contact dermatitis. Other cell types that may contribute include B-cells and hapten-specific IgM. Additionally, epidermal Langerhans cells have been ascribed an indispensable role as an antigen presenting cell to educate T-cells of the skin immune system. Studies of mice that lack this cell type suggest that Langerhans cells may be dispensible, and may even play a regulatory role in allergic contact dermatitis. The identity of the antigen presenting cells that complement Langerhans cells has yet to be identified. Lastly, Keratinocytes play a role in all phases of allergic contact dermatitis, from the early initiation phase with the elaboration of inflammatory cytokines, that plays a role in Langerhans cell migration, and T-cell trafficking, through the height of the inflammatory phase with direct interactions with epidermotrophic T-cells, through the resolution phase of allergic contact dermatitis with the production of anti-inflammatory cytokines and tolerogenic antigen presentation to effector T-cells. As the understanding of allergic contact dermatitis continues to improve, this will provide novel therapeutic targets for immune modulating therapy.

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Section: Kc: a Key Participant In Acdsupporting

confidence: 81%

Allergic Contact Dermatitis

Gober¹,

Gaspari²

2008

Current Directions in Autoimmunity

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“…Previous studies have shown that keratinocytes can affect T H cell responses to contact allergens via differential expression of costimulatory molecules. 33 This indicates close interaction between keratinocytes and T cells in the skin during ACD, where cytokine-mediated signaling also plays a role in the inflammatory process. Indeed, keratinocyte-derived IL-23 has been shown to affect cutaneous immune responses using transgenic mice constitutively expressing IL-12p40 in keratinocytes.…”

Section: Discussionmentioning

confidence: 97%

“…31,32 Furthermore, keratinocytes have the capacity to modulate T H cell responses to contact allergens in ACD via costimulatory molecules. 33 Thus we hypothesized that keratinocytes would produce IL-23 in response to contact allergens, and hence have the ability to promote T H 17-mediated skin inflammation in ACD. IL-23 and IL-12 are members of the same cytokine family and share the IL-12p40 subunit in combination with the IL-23p19 and IL12p35 subunits, respectively.…”

Section: Keratinocytes Produce Il-23 In Response To Nickelmentioning

confidence: 99%

IL-23 and TH17-mediated inflammation in human allergic contact dermatitis

Larsen

Bonefeld

Poulsen

et al. 2009

Journal of Allergy and Clinical Immunology

143

105

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“…575309), and samples were run according to the manufacturer's protocol for cell culture supernatants. DNFB-specific IgG2a serum ELISA was run as previously described (25). Briefly, serum was collected from contact hypersensitivity (CHS) mice 21 d after initial sensitization.…”

Section: Cytokine Elisamentioning

confidence: 99%

Ultraviolet Radiation Signaling through TLR4/MyD88 Constrains DNA Repair and Plays a Role in Cutaneous Immunosuppression

Harberts

Zhou

Fishelevich

et al. 2015

The Journal of Immunology

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UV radiation (UVR) induces DNA damage, leading to the accumulation of mutations in epidermal keratinocytes and immunosuppression, which contribute to the development of nonmelanoma skin cancer. We reported previously that the TLR4–MyD88 signaling axis is necessary for UV-induced apoptosis. In the dinitrofluorobenzene contact hypersensitivity model, UV-irradiated MyD88-deficient (MyD88−/−) C57BL/6 mice had intact ear swelling, exaggerated inflammation, and higher levels of dinitrofluorobenzene-specific IgG2a compared with wild-type (WT) mice. Even with normal UV-induced, dendritic cell migration, DNA damage in the local lymph nodes was less pronounced in MyD88−/− mice compared with WT mice. Cultured, UV-irradiated WT APCs showed cleavage (inactivation) of the DNA damage–recognition molecule PARP, whereas PARP persisted in MyD88−/− and TLR4−/− APCs. Epidermal DNA from in vivo UV-irradiated MyD88−/− mice had an increased resolution rate of cyclobutane pyrimidine dimers. Both in vitro treatment of MyD88−/− APCs with and intradermal in vivo injections of PARP inhibitor, PJ-34, caused WT-level cyclobutane pyrimidine dimer repair. Lymphoblasts deficient in DNA repair (derived from a xeroderma pigmentosum group A patient) failed to augment DNA repair after MyD88 knockdown after UVR, in contrast to lymphoblasts from a healthy control. These data suggest that interference with the TLR4/MyD88 pathway may be a useful tool in promoting DNA repair and maintaining immune responses following UVR-induced damage.

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Keratinocyte-derived, CD80-mediated costimulation is associated with hapten-specific IgE production during contact hypersensitivity to TH1 haptens

Cited by 18 publications

References 41 publications

Allergic Contact Dermatitis

Allergic Contact Dermatitis

IL-23 and TH17-mediated inflammation in human allergic contact dermatitis

Ultraviolet Radiation Signaling through TLR4/MyD88 Constrains DNA Repair and Plays a Role in Cutaneous Immunosuppression

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